About vision
Retinal cells embedded in the eyes have been grown in Russia
The technology will become the basis for the revolutionary treatment of glaucoma
Anna Urmantseva, Maria Nedyuk, Izvestia
MIPT scientists in collaboration with Harvard researchers have grown retinal cells that can grow into the eyes. This is the first successful attempt in the world to transplant ganglion cells (retinal neurons that are destroyed in glaucoma) obtained from stem cells in the laboratory. Next, the grown cells will need to be transplanted into the retina. Scientists tested the technology on mice and made sure of the successful embedding of cells and their survival throughout the year. In the future, the researchers plan to create specialized cell banks that will allow individually selecting therapy for each patient.
Operation "Transplantation"
The first successful attempt in the world to grow and transplant retinal ganglion cells from stem cells was made by scientists from the MIPT Genomic Engineering Laboratory in collaboration with researchers from Harvard Medical School. Ganglion cells are responsible for the transmission of visual information, and they are the ones that are damaged in glaucoma. Scientists managed not only to grow neurons (ganglions are considered specialized neurons), but also to transplant them into the eyes of mice, achieving the correct ingrowth of artificial retinal tissue. As is known, without treatment, the development of glaucoma can lead to irreversible damage to part of the optic nerve and, as a result, the loss of part of the visual field. Progressing over time, this disease can lead to complete blindness.
Retinal cells were grown in special organoids, the tissue was formed in a test tube, Evgeny Kegeles, a junior researcher at the MIPT Laboratory of Genomic Engineering, told Izvestia. Then these cells were transplanted to mice, which were distributed into several groups.
– There were mice with a glaucoma model, mice with increased intraocular pressure and those who had their own ganglions removed, – said Evgeny Kegeles. – There were also newborn mice: we tested the hypothesis of a more successful survival of young ganglion cells in the developing retina. As a result, it turned out that the cells have embedded and sprouted axons that will connect the eye with the brain. Improved cell survival in newborn mice gives us a promising direction for finding the best microenvironment.
According to Evgeny Kegeles, these cells successfully existed inside the retina for 12 months, which is a serious period for such a study. Scientists have managed to make sure that they receive visual signals, but the fact that cells transmit signals to the brain cannot be confirmed with absolute certainty yet.
– We know for sure that the grown cells are embedded in the right place, stretch axons into the brain, but it is impossible to evaluate their functionality yet, – explained Evgeny Kegeles. – This is due to the fact that so far we have not been able to grow a large number of cells. This is a matter of the next few years.
According to him, researchers need a year to be able to evaluate the functionality of cells in mouse models. During this time, it will be possible to obtain proof that the cells are not just properly embedded in the structure of the eye, but they "see".
Cell Bank
Now mouse retinal cells can be grown in about 21 days. In the case of a person, it will be from 50 to 100 days, MIPT scientists say.
However, most likely, a person with glaucoma preparing for transplantation will not need to grow retinal tissue from their own stem cells. Since the eye is an immunoprivileged organ, where rejections are rare, it is possible to create a cell bank for such patients. Either grown retinal cells from a universal donor or from induced pluripotent stem cells will be placed there. This means that it will be possible to grow cells in advance, freeze them and, when a glaucoma patient seeks help, choose the best cell option for transplantation for him.
Subsequently, this technology can be used to treat other eye diseases, for example, retinal dystrophy. However, other cells will have to be grown.
"The Nobel Prize for induced pluripotent stem cells was awarded almost 10 years ago, in 2012," said Pavel Volchkov, head of the Genomic Engineering Laboratory. – The so-called HYPE, when literally all scientific teams considered it their duty to deal with this topic, has long since faded away. Now is the time not just words, but real technologies based on iPSC (induced pluripotent stem cells – Izvestia). And it is precisely such technologies that the study on retinal ganglion transplantation belongs to. This is an opportunity to show that stem cells can really be put into practice, something can be fixed with their help. Although this work has not yet been brought to the clinic, but it is already a few steps away from a real transplant for the treatment of glaucoma.
Taking into account the extensive experience of experimental work of world scientists and the active study of the issue of cell replacement therapy in ophthalmology, in the future the method can lead to a breakthrough in the diagnosis and treatment of glaucoma, says Nika Takhchidi, head of the Department of Ophthalmology of the FSBI NMICO FMBA of Russia, a full member of the European Society of Cataract and Refractive Surgeons (ESCRS), a member of the Russian Society of Ophthalmologists.
– A number of foreign studies have shown that the injected cells are embedded in the retina and partially differentiate into retinal cells. Currently, two main mechanisms of cell action in vivo and in vitro are described and discussed. Replacement therapy is when cells formed as a result of differentiation of injected stem cells are "incorporated" into the tissue being restored. The "bystander effect" is when the injected stem cells have an anti–inflammatory, trophic or immunomodulatory effect on the tissue being restored. However, despite the breakthrough in the study of morphofunctional properties of stem cells, it is currently impossible to ensure guaranteed layer–by-layer replacement of damaged areas of the retina with cultured cells using the methods of administration practiced, which is confirmed by a number of experimental studies," Nika Takhchidi said.
However, many scientists in the world are now working in this direction, trying to create a cell therapy for the treatment of optic nerve atrophy, retinal dystrophy and glaucoma, said Irina Evsegneeva, head of the ophthalmology department of the Medsi Clinical Diagnostic Center, ophthalmologist.
– But there is no data to date that the transplanted cells transmit an image. Any idea how to do this deserves attention," she said.
According to the MIPT scientists, it will take about 10 years to bring the technology to use in medical practice.
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